The Role of Hsa_circ_0087862/miR-149-5p/TRAF6 Regulatory Axis in Colorectal Cancer Progression
摘要
Circular RNAs (circRNAs) have been reported to be associated with the progression of various tumors including colorectal cancer (CRC). However, the role and underlying mechanism of hsa_circ_0087862 in CRC remains unclear. Hsa_circ_0087862 expression in CRC tissues was analyzed using two GEO datasets (GSE138589 and GSE126094). Expression of hsa_circ_0087862, miR-149-5p and tumor necrosis factor receptor-associated factor 6 (TRAF6) in CRC cells was detected. The subcellular distribution of hsa_circ_0087862 was analyzed using a Cytoplasmic & Nuclear RNA Purification Kit. The function of hsa_circ_0087862 in CRC cells was detected using CCK-8, Transwell invasion assay, flow cytometry analysis, and Caspase-3 activity assay. The relationships between hsa_circ_0087862, miR-149-5p and TRAF6 were detected using luciferase reporter assay, RIP, or biotinylated RNA pull-down assay. Hsa_circ_0087862 was upregulated in CRC tissues and cells. Hsa_circ_0087862 is resistant to RNase R digestion and predominantly localized in the cytoplasm. Interference with hsa_circ_0087862 inhibited the malignant phenotypes of CRC cells by reducing cell proliferation and invasive abilities and triggering apoptosis. Hsa_circ_0087862 silencing inhibited TRAF6 expression by sponging miR-149-5p in CRC cells. Inhibition of miR-149-5p attenuated the effects of hsa_circ_0087862 on the malignant phenotypes of CRC cells. TRAF6 overexpression abolished the effects of miR-149-5p on cell growth, invasion and apoptosis in CRC cells. In conclusion, hsa_circ_0087862 silencing inhibited the malignant behaviors of CRC cells through inhibiting TRAF6 expression by sponging miR-149-5p.